Folate immobilized and PEGylated adenovirus for retargeting to tumor cells

Abstract

The surface of adenovirus (ADV) was modified with folate-poly(ethylene glycol) (FOL-PEG) conjugate to overcome the inherent problems associated with viral gene therapy. The ADV conjugated with FOL moieties at the distal end of PEG chains could not only reduce immune response, but also be retargeted to folate receptor overexpressing tumor cells. ADV coding the green fluorescent protein (GFP) gene was used to immobilize PEG or FOL-PEG conjugate on the surface to comparatively evaluate their extents of retargeting and immune response, as compared to those of naked ADV. The ADV conjugated with FOL-PEG exhibited a greatly enhanced level of GFP expression than naked or PEG immobilized ADV in a folate receptor overexpressing cell line (KB cells), but not in a folate receptor deficient cell line (A549 cells), suggesting that the retargeting of ADV could be achieved by immobilizing FOL-PEG conjugate. ADV immobilized with PEG or FOL-PEG also significantly lowered innate immune response, as judged from determining the amount of interleukin 6 released from macrophage.